dose-ranging study of st-920, an aav2/6 human alpha galactosidase a gene therapy in subjects with fabry disease (staar)

Conditions: Fabry Disease

Summary: this is the first in human treatment with st-920, a recombinant aav2/6 vector encoding the cdna for human a-gal a. the purpose of this study is to evaluate the safety and tolerability of ascending doses of st-920. st-920 aims to provide stable, long-term production of α-gal a at therapeutic levels in subjects with fabry disease. the constant production of α-gal a in humans should, importantly, enable reduction and potentially clearance of fabry disease substrates gb3 and lyso-gb3. on day 1, patients will be infused intravenously with a single dose of st-920 and followed for a period of 52 weeks.


Eligibility criteria:
inclusion criteria: * ≥ 18 years of age * documented diagnosis of fabry disease * one or more of the following symptoms: i) cornea verticillata, ii) acroparesthesia, iii) anhidrosis, iv) angiokeratoma * subject must be fully vaccinated (as per the centers for disease control and prevention (cdc) definition in the us and as per local guidelines in other countries) for covid-19 at least one month prior to dosing additional inclusion criteria: renal cohort: * screening egfr value between 40-90 ml/min/1.73 m² * linear negative egfr slope (estimated from at least 3 serum creatinine values within 18 months, including the value obtained during screening visit) of ≥ 2 ml/min/1.73m²/year cardiac cohort: • left ventricular hypertrophy (lvh) in 2d echocardiography or cmr defined as an end diastolic septum and posterior wall thickness ≥12 mm with no other explanation for lvh, or presentation with cardiac changes indicative of disease progression such as decreased global longitudinal strain on 2d strain echocardiography or low native t1 mapping on cmr exclusion criteria: * neutralizing antibodies to aav6 * egfr \< 40 ml/min/1.73m2 * new york heart association class iii or higher * active infection with hepatitis a, b or c, hiv or tb * history of liver disease such as clinically significant steatosis, fibrosis, non-alcoholic steatohepatitis (nash) and cirrhosis, biliary disease within 6 months of informed consent; except for gilbert's syndrome * elevated circulating serum afp * recent or recurrent hypersensitivity response to ert within within 6 months prior to consent * current or history of systemic (iv or oral) immunomodulatory agents, or biologics or steroid use in the past 6 months prior to consent (topical treatment and inhaled allowed). * contraindication to use of corticosteroids * history of malignancy except for non-melanoma skin cancer and localized prostate cancer treated with curative intent * recent history of alcohol or substance abuse * participation in investigational interventional drug or medical device study throughout the duration of this study and within previous 3 months prior to consent * prior treatment with a gene therapy product * known hypersensitivity to components of st-920 formulation * any other reason that, in the opinion of the site investigator or medical monitor, would render the subject unsuitable for participation in the study including but not limited to risk of covid-19 infection additional exclusion criteria for: renal cohort: * history of renal dialysis or transplantation * history of acute kidney insufficiency in the 6 months prior to screening * angiotensin converting enzyme (ace) inhibitor or angiotensin receptor blocker (arb) therapy initiated within 4 weeks prior to screening or changed ace inhibitor or arb dose in the 4 weeks prior to screening * urine protein to creatinine ratio (upcr) \> 0.5 g/g who are not being treated with an ace inhibitor or arb cardiac cohort: * significant cardiac fibrosis defined by late gadolinium enhancement on cmr * any contraindications to cmr as per local hospital/institution guidelines * angiotensin converting enzyme (ace) inhibitor or angiotensin receptor blocker (arb) therapy initiated within 4 weeks prior to screening or changed ace inhibitor or arb dose in the 4 weeks prior to screening * nyha class iv

Keywords: sangamo rare lysosomal storage disease gene therapy